Hi guys, my name is Paz Meyers, and I am a rising sophomore at Pierrepont School in Westport, Connecticut. I am interested in all things STEM, especially Biology, and when I first took Bio in 7th grade, my favorite unit was Genetics, which continues to be the area of biology that fascinates me the most. I also have a passion for languages, and am taking classical Greek and Latin, as well as Mandarin Chinese in school. Outside of the classroom, I am a serious cellist in an orchestra, string quartet, and as a soloist, and I love music and consider it to be another language that expresses what words cannot, in addition to a great way to meet cool people and travel to exciting places. I have also been swimming competitively for the past several years (mostly fly and free), and have played water polo, and am a (Pittsburgh) fan of most other sports. I am looking forward to three great weeks!




Computational applications of Synthetic Biology:
By Paz Meyers


Background:
Despite many advancements in technology, computers still have many problems and plenty of room for improvement. Computers are expensive, and building them often requires components that are dwindling in supply and rising in price. They are also usually incapable of operating in harsh environments where they are sometimes necessary. There is need for alternative solutions in building and operating computers.


Synthetic Biology offers lots of promise for both replacing computer components and performing computational tasks. While this field is still extremely new and developing, many developments have already been made in finding a way to use biology’s natural hardware for computational productivity. Especially in performing a main computer function of transmitting information, more problems than solutions are currently available for creating more complex computers.


Basic Computer Functions and Possibilities for Synthetic Biology Solutions:
Primary Computer Function #1; Storage of Information:
Using SynBio to perform this computer function of information storage is the closest to becoming a successful application of SynBio for computing purposes. DNA is biology’s hardware for information storage, as it contains the massive amounts of genetic material necessary for the synthesis of every amino acid in sequence to form proteins. It is the overwhelming capacity of DNA for information storage that makes it an ideal, potentially better if cost-effective, alternative to electronic data storage. Researchers at Harvard Wyss Institute and Columbia University have managed to synthesize data-storing DNA with capacities of 700 terabytes per gram and 215 petabytes per gram respectively, using the following method:


First, the data to be stored is converted to binary form by computer, and then to DNA base pair form, with an A/T letter pair corresponding to 0, and a G/C pair corresponding to 1, also done by computer. The sequence of pairs containing the data is then cut into segments, and a barcode-like identifying sequence placed at the beginning for identification and reassembly later. These sequences are then artificially synthesized, and contain the data along with the identifier sequences for reassembly.


To retrieve the data from the DNA, the DNA segments are sequenced, using the same process as for genomes, and the resulting sequences identified using an algorithm to read the “barcodes” and piece them together to reform the data. Once converted back into binary by computer, the data has been retrieved and is ready for use.


The researchers at both organizations who conducted these experiments completed this process without error, and retrieved and viewed their data. The reason for the higher storage efficiency achieved by Dr. Erlich at Columbia is that he had a higher ratio of data-containing segments to identifier sequence length than the researchers at the Wyss Institute. Theoretically, DNA has an even larger capacity for data storage, although currently it is yet to be reached.


Primary Computer Function #2; Logical Operations:
The second main function of a computer processor is to perform logical operations, and this is how the computer performs computations. Researchers at many different institutions have had success genetically engineering transcription-based logic gates, in which the presence or absence of certain compounds influences whether or not transcription takes place. The next development necessary for making these logic gates computationally productive is “wiring” them together so they can perform more advanced computations, closer to the complexity level of electronic processors.


Theoretically, if properly genetically engineered, multiple logic gates can connect within a single cell, with the outputs (boolean 1s or 0s) being the inputs for other logic gates within the same cell. The figure below shows an electronic full adder circuit, the basic unit necessary for the creation of an ALU (arithmetic logic unit) as used in electronic processors today:


Screen Shot 2017-07-13 at 9.34.43 AM.png
Screen Shot 2017-07-13 at 9.34.43 AM.png

This device is constructed by feeding three inputs, A, B, and Cin (carry in), through two XOR gates, two AND gates, and an OR gate, wired together to create two outputs, S (sum) and Cout (carry out). This device when made electronically requires 18 transistors, but using the design in the figure below could be contained in a single genetically modified cell:


Screen Shot 2017-07-13 at 9.41.59 AM.png
Screen Shot 2017-07-13 at 9.41.59 AM.png



In this design, the electronic multiple-transistor logic gates are replaced by genetically engineered transcription gates whose boolean inputs are the presence or absence (1 or 0) of the proteins represented by the circles on the left side of the gate. Depending on whether a given logic gate allows transcription to occur, its’ output protein will or will not be synthesized, representing either a 1 or a 0 in boolean. Below is a truth table for every potential input combination for this SynBio full adder device, and each input combination’s corresponding intermediate gate output and device output:


Screen Shot 2017-07-13 at 9.57.17 AM.png
Screen Shot 2017-07-13 at 9.57.17 AM.png




The full adder application of genetic logic gates is one of many potential uses of SynBio to perform logical functions. Other examples of potential applications, both simpler and more complicated than making an ALU, include making synthetic kidneys, leukemia-detecting bacteria that inhabit the bloodstream, cholera-sensing and killing bacteria, and others. Transcription-controlling logic gates have enormous potential to be computationally productive, and will become extremely useful in the future.


Primary Computer Function #3; Transmitting Information:
This third and final extremely important primary computer function has proved to have the most obstacles in the way of using SynBio to be computationally productive. Organisms are naturally quite communicative, but almost always on a much larger level than is useful for computational productivity. However, there are several possible solutions to this problem, but they are largely hypothetical, have many complications, and are very far from becoming reality:


One possible way of harnessing biological systems to be productive in transferring information in a computational sense is by using their quorum sensing behavior. Certain species of bacteria emit autoinducers and based on the quantity of those autoinducers present in the vicinity are able to determine whether or not there is a quorum of that species in the area and change to group behavior. A possible modification of this to be computationally productive would be to genetically engineer colonies of bacteria to output their binary result of their computation as autoinducers. Another colony would then detect that and its’ group behavior would be to perform the next computation. If this were to be feasible, here is how it would apply to the full adder application from the Logical Operations section:


Screen Shot 2017-07-13 at 11.38.39 AM.png
Screen Shot 2017-07-13 at 11.38.39 AM.png



In this diagram, the large green circles represent bacterial colonies, and each different colored small shape represents a different compound whose presence/absence would be the binary output of that colony’s full adder function. Enabling only 4 SynBio full adders to communicate would require separate genetic engineering of all four colonies, as well as 17 different compounds total produced or received by the system, which provides lots of opportunity for complication, and is a decently large amount of genetic engineering work. Due to these issues using quorum sensing is not a viable solution.


Another possible solution to the problem of how to transmit information is attempting to use basic bacterial communication to transmit information from cell to cell. Bacteria communicate by emitting compounds that signal to nearby bacteria information about the surroundings. Theoretically, one cell’s computed output could be the next cell’s input, but there is no way of controlling which surrounding cells receive this information. Unless each cell (or colony) were to be genetically engineered differently in sequence, alternative solutions would be necessary for productive communication between these cellular computers.


Finally, another more far-fetched possible solution for transmitting information is the usage of bacterial nanowires. Bacterial nanowires are tiny “wires” produced by certain bacteria to get rid of electrons by transferring them to other nearby cells, creating a kind of communal breathing apparatus. The important discovery about them for scientists is their ability to conduct electricity, and some scientists theorize that they may be a communication device for these bacteria, although that has not yet been proven. If they did in fact help with inter-cellular communication, that may be useful for computing applications.


Summary:
Synthetic biology is a relatively young field of research, and research on computational applications for it even younger, but there is great potential for significantly useful applications in computing. As of now, nobody has succeeded in making a full biological computer, but new research and discoveries are helping us get closer to that goal. There are many unanswered questions regarding how that will be achieved, and likely even more questions that we do not even know about yet, but if answered, biological computers may be a large part of the future of technology.


Sources:
__http://www.nature.com/news/how-to-turn-living-cells-into-computers-1.12406__
__http://www.openwetware.org/wiki/CH391L/S13/QuorumSensing__
__http://science.sciencemag.org/content/340/6132/599.full__
__https://www.sciencedaily.com/releases/2013/02/130207074254.htm__
__https://io9.gizmodo.com/this-new-discovery-will-finally-allow-us-to-build-biolo-462867996__
__http://www.sciencemag.org/news/2017/03/dna-could-store-all-worlds-data-one-room__
__http://science.howstuffworks.com/life/cellular-microscopic/bacteria-communication.htm__
[[https://en.wikipedia.org/wiki/Transistor–transistor_logic|https://en.wikipedia.org/wiki/Transistor–transistor_logic]]
__http://nanobio.kaist.ac.kr/lectures/BiS_673/2016_Notes/Handout%201_BE%20Introduction.pdf__
__http://www.kurzweilai.net/bacteria-communicate-and-exchange-energy-via-nanowires__
https://www.youtube.com/watch?v=7ukDKVHnac4



The link to my powerpoint presentation is below:
https://docs.google.com/presentation/d/1dX0-HU8tf2lECpUgi8wu6p1kKTlH64Os-wBO1eGpwzk/edit?usp=sharing